Senescent human diploid cells seem to possess a senescent factor which is dominant for growth and which inhibits nuclear DNA synthesis in hybrid cells. We shall determine the intracellular location of the senescent factor by determining the growth potential of cells reconstituted from cytoplasts of young cells and karyoplasts of senescent cells and the growth potential of cells reconstituted from cytoplasts of senescent cells and karyoplasts of young cells. Cells deficient in hypoxanthine guanine phosphoribosyl transferase (HPRT minus) and cells having this enzyme. Reconstituted cells will be selectively grown in medium containing either thioguanine or hypoxanthine, aminopterin, and thymidine. The growth potential of both populations and of individual cells will be determined. We shall examine the intracellular location of the factor which inhibits nuclear DNA synthesis in hybrid cells by fusing cytoplasts and karyoplasts of senescent cells to young diploid cells. The fusion products will be exposed to tritiated thymidine and the pattern of nuclear DNA synthesis examined by autoradiography. The results will indicate whether this factor is localized in the cytoplasm or the nucleus of senescent cells. We shall determine whether the prematurely aging phenotype of progeric and Werner's syndrome cells is dominant or recessive in hybrids with normal human diploid fibroblasts. We shall also determine whether progeric or Werner's syndrome cells inhibit nuclear DNA synthesis in heterokaryons with young, normal cells.